Canine ocular onchocerciasis: a retrospective review of the diagnosis, treatment, and outcome of 16 cases in New Mexico (2011-2015).

OBJECTIVE: To describe the clinical exam findings, treatment and outcomes of 16 dogs diagnosed with ocular onchocerciasis in New Mexico. MATERIALS AND METHODS: Records of dogs diagnosed by the primary author were reviewed (2011-2015). Records that were accessible and included a diagnosis of Onchocerca lupi by histopathologic or molecular identification of the nematode were included. RESULTS: Sixteen cases were included. 3/16 dogs were treated with year-round heartworm prophylaxis prior to infection. Clinical exam findings included conjunctival hyperemia and/or episcleral injection (16/16), focal subconjunctival mass(es) (14/16), retinal detachment (7/16), corneal edema (4/16), chemosis (3/16), corneal opacity (2/16), exophthalmia (1/16), glaucoma (1/16), strabismus (1/16), blepharospasm (1/16), and vitreal degeneration (1/16). Ocular involvement was unilateral in 7/16 dogs and bilateral in 9/16 dogs. The diagnosis was confirmed via histologic identification of the nematodes and/or PCR. Treatment consisted of medical management or a combination medical and surgical management. Known or suspected recurrence of disease was documented in 10 dogs. CONCLUSIONS: Canine ocular onchocerciasis is endemic in New Mexico. Histopathology and molecular identification are useful diagnostic tools. Medical management alone was successful in many cases.

Ocular onchocerciasis in the Yanomami communities from Brazilian Amazon: effects on intraocular pressure.

To determine the influence of onchocercal eye disease on the intraocular pressure of the Yanomami Tribe Aratha-ú of Roraima State, Brazil, considered endemic for onchocerciasis, a total of 86 patients were submitted to an ophthalmologic exam that included external examination, slit lamp examination, intraocular pressure measurement, and a fundus ophthalmoscope examination. A high prevalence of onchocerciasis-related eye lesions was encountered in 68.6% of the patients. Punctate keratitis and microfilariae in the anterior chamber were found in ∼28%. The mean of intraocular eye pressure found was 10.47 mm of Hg.

Progress toward elimination of onchocerciasis in the Americas - 1993-2012.

Onchocerciasis (river blindness) is caused by the parasitic worm Onchocerca volvulus, transmitted to humans by the bite of infected black flies of the genus Simulium, and is characterized by chronic skin disease, severe itching, and eye lesions that can progress to complete blindness. Currently, among approximately 123 million persons at risk for infection in 38 endemic countries, at least 25.7 million are infected, and 1 million are blinded or have severe visual impairment. Periodic, communitywide mass drug administration (MDA) with ivermectin (Mectizan, Merck) prevents eye and skin disease and might interrupt transmission of the infection, depending on the coverage, duration, and frequency of MDA. The Onchocerciasis Elimination Program for the Americas (OEPA) was launched in response to a 1991 resolution of the Pan American Health Organization (PAHO) calling for the elimination of onchocerciasis from the Americas. By the end of 2012, transmission of the infection, judged by surveys following World Health Organization (WHO) guidelines, had been interrupted or eliminated in four of the six endemic countries in the WHO Americas Region. Thus, in 2013, only 4% (23,378) of the 560,911 persons originally at risk in the Americas will be under ivermectin MDA. Active transmission currently is limited to two foci among Yanomami indigenes in adjacent border areas of Venezuela and Brazil.

The Carter Center's assistance to river blindness control programs: establishing treatment objectives and goals for monitoring ivermectin delivery systems on two continents.

Periodic mass treatment with ivermectin in endemic communities prevents eye and dermal disease due to onchocerciasis. As part of an international global partnership to control onchocerciasis, The Carter Center's Global 2000 River Blindness Program (GRBP) assists the ministries of health in ten countries to distribute ivermectin (Mectizan, donated by Merck & Co.). The GRBP priorities are to maximize ivermectin treatment coverage and related health education and training efforts, and to monitor progress through regular reporting of ivermectin treatments measured against annual treatment objectives and ultimate treatment goals (e.g., full coverage, which is defined as reaching all persons residing in at risk villages who are eligible for treatment). Since the GRBP began in 1996, more than 21.2 million ivermectin treatment encounters have been reported by assisted programs. In 1999, more than 6.6 million eligible persons at risk for onchocerciasis received treatment, which represented 96% of the 1999 annual treatment objective of 6.9 million, and 78% of the ultimate treatment goal in assisted areas.

The Onchocerciasis elimination program for the Americas: a history of partnership

The decision in 1987 by the pharmaceutical firm Merck & Co. to provide Mectizan (ivermectin) free of charge to river blindness control programs has challenged the international public health community to find effective ways to distribute the drug to rural populations most affected by onchocerciasis. In the Americas, PAHO responded to that challenge by calling for the elimination all morbidity from onchocerciasis from the region by the year 2007 through mass distribution of ivermectin. Since 1991, a multinational, multiagency partnership (consisting of PAHO, the endemic countries, nongovernmental development organizations, the Centers for Disease Control and Prevention in Atlanta, Georgia, as well as academic institutions and funding agencies) has developed the political, financial, and technical support needed to move toward the realization of that goal. This partnership is embodied in the Onchocerciasis Elimination Program for the Americas (OEPA), which is supported by the River Blindness Foundation (RBF) and now by the Carter Center, OEPA was conceived as a means of maintaining a regional initiative to eliminate what is otherwise a low priority disease. Since its inception in 1993, the OEPA has provided more than US$ 2 million in financial, managerial, and technical assistance to stimulate and/or support programs in Brazil, Colombia, Ecuador, Guatemala, Mexico, and Venezuela, so as to take full advantage of the Merck donation, Now halfways into a five-year, US$ 4 million grant provided through the Inter-American Development Bank, the OEPA's capacity to support the regional initiative is assured through 1999 (AU)

Onchocerciasis in Ecuador: evolution of chorioretinopathy after amocarzine treatment.

AIMS: To investigate the impact of the macrofilaricidal drug, amocarzine, on the evolution of chorioretinopathy in onchocerciasis. METHODS: A prospective uncontrolled cohort study was performed using subjects infected with Onchocerca volvulus in a hyperendemic onchocerciasis focus in Esmeraldas Province in Ecuador. Study subjects were recruited into four cohorts in which ophthalmic and parasitological data were collected for 2, 3, 4, and 5 years respectively. RESULTS: Complete ophthalmic follow up was obtained for 294 individuals in the four cohorts. The incidence of retinal pigment epithelial atrophy tended to remain constant between cohorts while that of chorioretinal scarring with a greater observation period. The incidence rate of cases with new or extending chorioretinal lesions was greater with an increasing period of follow up. An association was seen between the cumulative microfilarial loads in the skin and the development of new chorioretinal lesions (p < 0.05). No relation was noted between cumulative microfilarial loads and the progression of existing disease. CONCLUSION: Amocarzine therapy did not prevent the natural evolution of chorioretinal disease. It was suggested that ocular microfilariae were necessary for the induction of chorioretinopathy in previously unaffected eyes and that extension of existing disease might also be related to the presence of ocular microfilariae or to other immunological mechanisms.

Effect of semiannual treatments of ivermectin on the prevalence and intensity of Onchocerca volvulus skin infection, ocular lesions, and infectivity of Simulium ochraceum populations in southern Mexico.

The effect of semiannual ivermectin treatment along with nodulectomy on filarial transmission levels were estimated during the three dry seasons of 1991-1993 in a hyperendemic village in southern Mexico. Parasitologic and ophthalmologic examinations were carried out every six months until five drug treatments were completed. Ivermectin mass treatment with a coverage of approximately 80% had a significant impact (P < 0.05) on the prevalence of skin infection and the mean microfilarial skin density (CMFL), which were reduced 38% and 89%, respectively. A gradual and significant (P < 0.05) decrease in the mean microfilariae number in the anterior chamber of the eye and in corneal opacities was also observed as the CMFL was reduced. After three treatments, these were reduced 84% and 69%, respectively. However, after two years of continuous intervention, no significant differences (P > 0.05) were observed in either the daily mean infective biting density and the daily mean transmission potential. This was probably due to the remaining microfilarial load provided by the untreated resident population and migrant groups. On the whole, our results confirm both the efficacy of ivermectin to alleviate the clinical manifestations of the disease and its minimal impact on Onchocerca volvulus transmission, and indicate the need both to achieve higher levels of drug coverage and to incorporate other measures to stop transmission until a macrofilaricide drug is found.

Albendazole in the treatment of onchocerciasis: double-blind clinical trial in Venezuela.

A double-blind clinical trial was conducted in Monagas State, Venezuela to assess the tolerance and efficacy of albendazole in the therapy of Onchocerca volvulus infection. Forty-nine patients (26 treated and 23 controls) received a 10-day course of albendazole (400 mg/day) or a placebo. Consistent with the excellent tolerance observed, albendazole did not kill microfilariae. However, analysis of changes in microfilarial densities (mf/mg of skin) over one year showed that albendazole was active against O. volvulus, presumably by interfering with embryogenesis. The nature, degree, and duration of this effect remain to be determined.

Amocarzine investigated as oral onchocercacidal drug in 272 adult male patients from Guatemala. Results from three dose regimens spread over three days.

The clinical investigations with three types of a three days regimen of amocarzine permitted to adjust the fixed dosing to the body weight related dosing and subsequently the administration of amocarzine from fasting state to drug intake after food. The main objective to reach a dose with predictable and sustained absorption was achieved, and this in turn proved to be onchocercacidal and safe. A combined clinicopharmacokinetic study showed enhancement and consistency of amocarzine absorption after food. Quantitative assessment of the urinary excretion confirmed the presence of the N-oxide metabolite, which qualitatively was visible by a urine colorimetry. This assay proved useful for drug monitoring. Ultrasonography of onchocercal skin nodules detected changes within the nodules following amocarzine therapy. Histology after nodul-ectomy at four months post-therapy showed that 57% of the female worms were dead, 24% necrobiotic, and 19% alive; male worms were more necrobiotic. Skin microfilariae were reduced within one week to about 10% of the initial level and after one year they remained at about 20%. Skin punch biopsies on day 5 showed that most microfilariae were dead or moribund. Ocular reduction of microfilariae was also observed, although it was slower than in the skin. The visual acuity improved within the one year's observation time. Ocular and clinical tolerability was good, with one exception of neurological disturbance, which was fully reversible. Sequential testing of the liver function showed average values within the normal range. In conclusion, a repeat low dose regimen of amocarzine (3 mg/kg twice daily post-prandially for three consecutive days) was well absorbed with predictable plasma levels, macro- and microfilaricidal with good local and systemic tolerability in patients with moderate to heavy onchocerciasis. Amorcarzine is recommended for further clinical investigations, particularly in females and juveniles. Urine colorimetry and nodular ultrasonography are recommended for optional monitoring of amocarzine.

Onchocercacidal effect of three drug regimens of amocarzine in 148 patients of two races and both sexes from Esmeraldas, Ecuador.

The objective of this multidisciplinary clinical investigation was to test whether amocarzine was absorbed effectively and safely in patients of two races and either sex infected with Onchocerca volvulus while living in the holoendemic area of Esmeraldas Province, Ecuador. The prerequisite for a systemic onchocercacidal effect is the regular absorption of orally administered amocarzine. Single dosing after overnight fasting proved to produce irregular absorption of amocarzine, although some microfilaricidal effect was achieved. A pilot study with repeated low dose and postprandial administration of amocarzine showed a regular and predictable absorption with acceptable tolerability and a microfilaricidal effect lasting up to one year post-therapy. Since amocarzine and its major N-oxide metabolite are coloured agents, urine colorimetry was used to assess the urinary excretion of the N-oxide qualitatively. For the postprandial drug regimens plasma concentrations of amocarzine and its metabolite were determined at two selected time points in patients of two races and either sex; the results showed no major differences. Excision of onchocercal nodules was performed four months post-therapy. The pooled results of the histologic analysis of 100 patients with the same drug regimen read under blinded condition showed that 65% of the adult female worms were dead, 20% necrobiotic and 15% alive. The male worms were fewer and mainly necrobiotic. Control worm populations in Esmeraldas without chemotherapy showed that on the average 81.5% were alive and 18.5% dead. Amocarzine was also microfilaricidal producing a reduction of skin dwelling microfilariae to about 10% of the initial value within the first week after start of therapy and lasting for half a year at a 20% level. The reduction of ocular microfilarial was slower and reached 35-40% after one year. The general tolerability was acceptable to good. Reversible dermal reactions were usually mild and peaked as a rash in 57% of the patients on day 6. No prohibitive ocular intolerance was observed. Mild and reversible dizziness peaked on day 4 in 74% of patients. A positive reversible Romberg sign was found in 12 patients on day 4. Amocarzine, the first oral micro- and macrofilaricidal agent administered as a low dose repeat regimen (3 mg/kg twice daily and postprandial for three consecutive days) can be recommended for oral onchocercacidal therapy in adult patients. Clinical trials in juveniles should be encouraged.